Deoxyribo- and ribooligonucleotides derived from guanosine (dG and G) and from cytidine (dC) are being synthesized via the cyclic enediol phosphoryl (CEP) method. The first nucleoside is protected at 5'-OH and the base-NH2 groups, and is quantitatively "CEP-ylated" at the 3'-OH by 1,2-dimethylethenylenephosphoro-chloridate (CEP-Cl). The product is "coupled with the 5'-OH of the second nucleoside having free 3'-OH and protected base-NH2 group (in the deoxyriboseries), or free 3'-OH and protected 2'-OH and base-NH2 group (in the riboseries). The resulting phosphotriester has the l-methylacetonyl phosphate-blocking group, which is stable toward acid but removable in aqueous triethylamine or ammonia. The method has been standardized, up to the tetramer stage, with these protecting groups: monomethoxytrityl at 5'-OH; t-butyldimethylsilyl at 2'-OH; and benzoyl or isobutyroyl at the base-NH2 groups of C and G, respectively. Trifluoroacetic acids removes only the 5'-protecting group from the triester, and the resulting dinucleotide triester can be used as the coupling component in block-polymerization with another 3'-CEP-ylated, 5'-protected dinucleotide triester to give the 5'-protected tetranucleotide triester. The final oligonucleotide salt is obtained by removal of the 5'-protection with acid, of the l-methylacetonyl and the base NH2-protection with aqueous ammonia, and in the ribo series of 2-silyl protection with fluoride ion. Work continues toward the preparation and isolation of substantial amounts of larger DNA and t-RNA segments based on dC, C, dG and G, and of certain unnatural oligonucleotides.